Ophthalmology (Eye & Ear Hospital) - Research Publications

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    Sustained and rebound effect of repeated low-level red-light therapy on myopia control: A 2-year post-trial follow-up study
    Xiong, R ; Zhu, Z ; Jiang, Y ; Kong, X ; Zhang, J ; Wang, W ; Kiburg, K ; Yuan, Y ; Chen, Y ; Zhang, S ; Xuan, M ; Zeng, J ; Morgan, IG ; He, M (WILEY, 2022-12)
    BACKGROUND: To evaluate the long-term efficacy and safety of continued repeated low-level red-light (RLRL) therapy on myopia control over 2 years, and the potential rebound effect after treatment cessation. METHODS: The Chinese myopic children who originally completed the one-year randomised controlled trial were enrolled. Children continued RLRL-therapy were defined as RLRL-RLRL group, while those who stopped and switched to single-vision spectacle (SVS) in the second year were RLRL-SVS group. Likewise, those who continued to merely wear SVS or received additional RLRL-therapy were SVS-SVS and SVS-RLRL groups, respectively. RLRL-therapy was provided by an at-home desktop light device emitting red-light of 650 nm and was administered for 3 min at a time, twice a day and 5 days per week. Changes in axial length (AL) and cycloplegic spherical equivalence refraction (SER) were measured. RESULTS: Among the 199 children who were eligible, 138 (69.3%) children attended the examination and 114 (57.3%) were analysed (SVS-SVS: n = 41; SVS-RLRL: n = 10; RLRL-SVS: n = 52; RLRL-RLRL: n = 11). The baseline characteristics were balanced among four groups. In the second year, the mean changes in AL were 0.28 ± 0.14 mm, 0.05 ± 0.24 mm, 0.42 ± 0.20 mm and 0.12 ± 0.16 mm in SVS-SVS, SVS-RLRL, RLRL-SVS and RLRL-RLRL group, respectively (p < 0.001). The respective mean SER changes were -0.54 ± 0.39D, -0.09 ± 0.55D, -0.91 ± 0.48D, and -0.20 ± 0.56D (p < 0.001). Over the 2-year period, axial elongation and SER progression were smallest in RLRL-RLRL group (AL: 0.16 ± 0.37 mm; SER: -0.31 ± 0.79D), followed by SVS-RLRL (AL: 0.44 ± 0.37 mm; SER: -0.96 ± 0.70D), RLRL-SVS (AL: 0.50 ± 0.28 mm; SER: -1.07 ± 0.69D) and SVS-SVS group (AL: 0.64 ± 0.29 mm; SER: -1.24 ± 0.63D). No self-reported adverse events, functional or structural damages were noted. CONCLUSIONS: Continued RLRL therapy sustained promising efficacy and safety in slowing myopia progression over 2 years. A modest rebound effect was noted after treatment cessation.
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    Retinal age gap as a predictive biomarker of stroke risk
    Zhu, Z ; Hu, W ; Chen, R ; Xiong, R ; Wang, W ; Shang, X ; Chen, Y ; Kiburg, K ; Shi, D ; He, S ; Huang, Y ; Zhang, X ; Tang, S ; Zeng, J ; Yu, H ; Yang, X ; He, M (BMC, 2022-11-30)
    BACKGROUND: The aim of this study is to investigate the association of retinal age gap with the risk of incident stroke and its predictive value for incident stroke. METHODS: A total of 80,169 fundus images from 46,969 participants in the UK Biobank cohort met the image quality standard. A deep learning model was constructed based on 19,200 fundus images of 11,052 disease-free participants at baseline for age prediction. Retinal age gap (retinal age predicted based on the fundus image minus chronological age) was generated for the remaining 35,917 participants. Stroke events were determined by data linkage to hospital records on admissions and diagnoses, and national death registers, whichever occurred earliest. Cox proportional hazards regression models were used to estimate the effect of retinal age gap on risk of stroke. Logistic regression models were used to estimate the predictive value of retinal age and well-established risk factors in 10-year stroke risk. RESULTS: A total of 35,304 participants without history of stroke at baseline were included. During a median follow-up of 5.83 years, 282 (0.80%) participants had stroke events. In the fully adjusted model, each one-year increase in the retinal age gap was associated with a 4% increase in the risk of stroke (hazard ratio [HR] = 1.04, 95% confidence interval [CI]: 1.00-1.08, P = 0.029). Compared to participants with retinal age gap in the first quintile, participants with retinal age gap in the fifth quintile had significantly higher risks of stroke events (HR = 2.37, 95% CI: 1.37-4.10, P = 0.002). The predictive capability of retinal age alone was comparable to the well-established risk factor-based model (AUC=0.676 vs AUC=0.661, p=0.511). CONCLUSIONS: We found that retinal age gap was significantly associated with incident stroke, implying the potential of retinal age gap as a predictive biomarker of stroke risk.
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    Diabetes mellitus and incident glaucoma in Australia: a 10-year cohort study from the 45 and Up Study
    Jiang, Y ; Xiao, G ; Han, X ; Zhu, Z ; Shang, X ; Xiong, R ; Scheetz, J ; Zhang, L ; Kiburg, KV ; He, M (AME PUBLISHING COMPANY, 2022-08)
    BACKGROUND: Understanding the relationship between diabetes mellitus (DM) and the severity of glaucoma is important for the primary prevention of incident glaucoma. This paper aims to examine the association between DM and incident glaucoma. METHODS: The 45 and Up Study is a prospective cohort study where Australians aged ≥45 years old were enrolled. The incident of glaucoma at follow-up is the main outcome measured. Glaucoma incidence was identified as those with recorded glaucoma-related medication from the Pharmaceutical Benefits Scheme or surgery recorded in the Medicare Benefits Schedule. Patients with glaucoma were classified into the medical glaucoma group (with glaucoma-related medication but not surgery) and the surgical glaucoma group (with glaucoma-related surgery). A Cox regression model was used to calculate the hazard ratios (HRs) to examine the association between baseline DM and the risk of developing glaucoma during the follow-up period. The reference groups are as follows: (I) non-DM participant; (II) participant with DM, duration between 0 and 5 years; (III) participant uses insulin. RESULTS: A total of 255,547 eligible participants, with no glaucoma diagnosis at baseline, were included. During the follow-up period, 7,667 patients (3.0%) were identified as medical glaucoma only and 2,326 patients (0.9%) underwent glaucoma surgery. After controlling for confounders, baseline DM was associated with an increased risk of glaucoma in the medical glaucoma group only [hazard ratio (HR) =1.36, 95% confidence interval (CI) =1.07-1.72, P=0.002]. However, baseline DM (HR =0.97, 95% CI =0.57-1.65, P=0.979) was not associated with an increased risk of surgical glaucoma. CONCLUSIONS: DM was associated with an increased risk of medical glaucoma only, there was no association identified with surgical glaucoma in the Australian population recruited in the 45 and Up Study.
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    Plasma metabolomic profiles of dementia: a prospective study of 110,655 participants in the UK Biobank
    Zhang, X ; Hu, W ; Wang, Y ; Wang, W ; Liao, H ; Zhang, X ; Kiburg, K ; Shang, X ; Bulloch, G ; Huang, Y ; Zhang, X ; Tang, S ; Hu, Y ; Yu, H ; Yang, X ; He, M ; Zhu, Z (BMC, 2022-08-15)
    BACKGROUND: Plasma metabolomic profile is disturbed in dementia patients, but previous studies have discordant conclusions. METHODS: Circulating metabolomic data of 110,655 people in the UK Biobank study were measured with nuclear magnetic resonance technique, and incident dementia records were obtained from national health registers. The associations between plasma metabolites and dementia were estimated using Cox proportional hazard models. The 10-fold cross-validation elastic net regression models selected metabolites that predicted incident dementia, and a 10-year prediction model for dementia was constructed by multivariable logistic regression. The predictive values of the conventional risk model, the metabolites model, and the combined model were discriminated by comparison of area under the receiver operating characteristic curves (AUCs). Net reclassification improvement (NRI) was used to estimate the change of reclassification ability when adding metabolites into the conventional prediction model. RESULTS: Amongst 110,655 participants, the mean (standard deviation) age was 56.5 (8.1) years, and 51 186 (46.3%) were male. A total of 1439 (13.0%) developed dementia during a median follow-up of 12.2 years (interquartile range: 11.5-12.9 years). A total of 38 metabolites, including lipids and lipoproteins, ketone bodies, glycolysis-related metabolites, and amino acids, were found to be significantly associated with incident dementia. Adding selected metabolites (n=24) to the conventional dementia risk prediction model significantly improved the prediction for incident dementia (AUC: 0.824 versus 0.817, p =0.042) and reclassification ability (NRI = 4.97%, P = 0.009) for identifying high risk groups. CONCLUSIONS: Our analysis identified various metabolomic biomarkers which were significantly associated with incident dementia. Metabolomic profiles also provided opportunities for dementia risk reclassification. These findings may help explain the biological mechanisms underlying dementia and improve dementia prediction.
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    Association between dual sensory impairment and risk of mortality: a cohort study from the UK Biobank
    Zhang, X ; Wang, Y ; Wang, W ; Hu, W ; Shang, X ; Liao, H ; Chen, Y ; Kiburg, KV ; Huang, Y ; Zhang, X ; Tang, S ; Yu, H ; Yang, X ; He, M ; Zhu, Z (BMC, 2022-08-01)
    BACKGROUND: Dual sensory impairment is affecting over 10% of older adults worldwide. However, the long-term effect of dual sensory impairment (DSI) on the risk of mortality remains controversial. We aim to investigate the impact of single or/and dual sensory impairment on the risk of mortality in a large population-based sample of the adult in the UK with 14-years of follow-up. METHODS: This population-based prospective cohort study included participants aged 40 and over with complete records of visual and hearing functions from the UK Biobank study. Measurements of visual and hearing functions were performed at baseline examinations between 2006 and 2010, and data on mortality was obtained by 2021. Dual sensory impairment was defined as concurrent visual and hearing impairments. Cox proportional hazards regression models were employed to evaluate the impact of sensory impairment (dual sensory impairment, single visual or hearing impairment) on the hazard of mortality. RESULTS: Of the 113,563 participants included in this study, the mean age (standard deviation) was 56.8 (8.09) years, and 61,849 (54.5%) were female. At baseline measurements, there were 733 (0.65%) participants with dual sensory impairment, 2,973 (2.62%) participants with single visual impairment, and 13,560 (11.94%) with single hearing impairment. After a follow-up period of 14 years (mean duration of 11 years), 5,992 (5.28%) participants died from all causes. Compared with no sensory impairment, dual sensory impairment was significantly associated with an estimated 44% higher hazard of mortality (hazard ratio: 1.44 [95% confidence interval, 1.11-1.88], p = 0.007) after multiple adjustments. CONCLUSIONS: Individuals with dual sensory impairment were found to have an independently 44% higher hazard of mortality than those with neither sensory impairment. Timely intervention of sensory impairment and early prevention of its underlying causes should help to reduce the associated risk of mortality.
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    Retinal age gap as a predictive biomarker of future risk of Parkinson's disease
    Hu, W ; Wang, W ; Wang, Y ; Chen, Y ; Shang, X ; Liao, H ; Huang, Y ; Bulloch, G ; Zhang, S ; Kiburg, K ; Zhang, X ; Tang, S ; Yu, H ; Yang, X ; He, M ; Zhu, Z (OXFORD UNIV PRESS, 2022-03-01)
    INTRODUCTION: retinal age derived from fundus images using deep learning has been verified as a novel biomarker of ageing. We aim to investigate the association between retinal age gap (retinal age-chronological age) and incident Parkinson's disease (PD). METHODS: a deep learning (DL) model trained on 19,200 fundus images of 11,052 chronic disease-free participants was used to predict retinal age. Retinal age gap was generated by the trained DL model for the remaining 35,834 participants free of PD at the baseline assessment. Cox proportional hazards regression models were utilised to investigate the association between retinal age gap and incident PD. Multivariable logistic model was applied for prediction of 5-year PD risk and area under the receiver operator characteristic curves (AUC) was used to estimate the predictive value. RESULTS: a total of 35,834 participants (56.7 ± 8.04 years, 55.7% female) free of PD at baseline were included in the present analysis. After adjustment of confounding factors, 1-year increase in retinal age gap was associated with a 10% increase in risk of PD (hazard ratio [HR] = 1.10, 95% confidence interval [CI]: 1.01-1.20, P = 0.023). Compared with the lowest quartile of the retinal age gap, the risk of PD was significantly increased in the third and fourth quartiles (HR = 2.66, 95% CI: 1.13-6.22, P = 0.024; HR = 4.86, 95% CI: 1.59-14.8, P = 0.005, respectively). The predictive value of retinal age and established risk factors for 5-year PD risk were comparable (AUC = 0.708 and 0.717, P = 0.821). CONCLUSION: retinal age gap demonstrated a potential for identifying individuals at a high risk of developing future PD.